DESCRIPTION: (Applicant's Abstract) This is a competitive renewal application to continue to study the efficacy of serotonergic medications in the outpatient treatment of cocaine dependence. The originally funded study examined tryptophan, the precursor of serotonin, in the treatment of cocaine abuse, and hence the grant was titled "Tryptophan and Behavior Therapy for Cocaine Abuse." Since this renewal shifts focus from tryptophan to another medication that alters serotonin functioning (fluoxetine), it has been re-titled "Serotonin Treatment of Cocaine Dependence." While several studies have reported on clinical experience in the use of fluoxetine for the treatment of cocaine use, most of these studies have methodological limitations (e.g., small sample sizes, heterogeneous study populations, failure to ensure compliance in taking medication, inadequate patient motivation). Importantly, there have now been several well conducted, controlled studies suggesting fluoxetine can be effective in the treatment of cocaine abuse - when medication compliance is assured, and when it is combined with incentives that provide motivation to stop using cocaine. Further, pilot subjects tested in our clinic with the currently proposed methods have shown positive responses. This proposal builds upon prior studies in its design and extends the methods used with our pilot subjects. It also continues the theme begun with the first study - that is, enhancing serotonergic functioning as a means of decreasing the reinforcing effects of cocaine. The current proposal again tests medication efficacy in the context of voucher incentives that provide motivation to stop cocaine use, but now has new design features in response to experience from the first clinical trial. Specifically, this proposal is to test fluoxetine in methadone maintained patients with concurrent cocaine dependence. There are several reasons for utilizing methadone maintained patients: compliance taking medication can be assured, retention rates are high, and concurrent cocaine dependence is common. The design is a 2 x 2, with patients randomly assigned to receive either double blind fluoxetine or placebo, and either voucher incentives or no voucher incentives. Voucher incentives can be effective in decreasing cocaine use, but studies have shown only about one-half of patients respond to this intervention. The main hypothesis to be tested in this study is that the combination of fluoxetine with vouchers will produce enhanced effects on decreasing cocaine use, compared to outcomes produced by the treatments alone. The principal logic underlying this study is that fluoxetine will weaken (but not necessarily eliminate) cocaine effects, and that this will translate into higher success rates under a behavior therapy that provides incentives for abstinence. These results will provide valuable new information about the ability of fluoxetine to enhance the effectiveness of an effective behavioral treatment intervention, and can lead to new and innovative treatment approaches for cocaine abusing patients.